Studies are proposed to specify the orientations of the sickle hemoglobin molecules in the 14 filaments of the fibers that occur in sickled cells. The principal approach will be to study artificial hemoglobin molecules with a second site mutation (in the alpha chains). Since various portions of the alpha chains lie at contacts between the filaments in the fibers and since there are several classes of structurally distinct contacts, single alpha chain mutations may be expected to interrupt one class of contacts. In this way certain regions of the hemoglobin surface can be localized to certain contacts and with sufficient information of this type the orientation of the hemoglobin molecules and stereochemistry of the contacts should be fully determined. Such knowledge should be useful in identifying potential targets for anti-sickling agents.